Vascular calcification (VC) is an urgent worldwide health issue with no available medical treatment. It is an active cell-driven process by osteogenic differentiation of vascular cells with complex mechanisms. The AMP-activated protein kinase (AMPK) serves as the master sensor of cellular energy status. Accumulating evidence reveals the vital role of AMPK in VC progression. AMPK is involved in VC in various ways, including inhibiting runt-related transcription factor 2 signaling pathways, triggering autophagy, attenuating endoplasmic reticulum stress and dynamic-related protein 1-mediated mitochondrial fission, and activating endothelial nitric oxide synthase. AMPK activators, like metformin, are associated with reduced calcification deposits in certain groups of patients, indicating that AMPK is a potential therapeutic target for VC.

BackgroundAberrant activation of fibroblast growth factor receptor 3 (FGFR3) is frequently observed in bladder cancer, but how it involved in carcinogenesis is not well understood. The current study was aimed to investigate the underlying mechanism on the progression of bladder cancer.MethodsThe GSE41035 dataset downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) between bladder cancer cell line RT112 with or without depletion of FGFR3, and gene ontology enrichment analysis was performed. Then, FGFR3-centered protein–protein interaction (PPI) and regulatory networks were constructed. Combined with the data retrieved from GSE31684, prognostic makers for bladder cancer were predicted.ResultsWe identified a total of 2855 DEGs, and most of them were associated with blood vessel morphogenesis and cell division. In addition, KIAA1377, POLA2, FGFR3, and EPHA4 were the hub genes with high degree in the FGFR3-centered PPI network. Besides, 17 microRNAs (miRNAs) and 6 transcriptional factors (TFs) were predicted to be the regulators of the nodes in PPI network. Moreover, CSTF2, POLA1, HMOX2, and EFNB2 may be associated with the prognosis of bladder cancer patient.ConclusionsThe current study may provide some insights into the molecular mechanism of FGFR3 as a mediator in bladder cancer.

Background: Metformin is the first-line antidiabetic medication for type 2 diabetes mellitus (T2DM). However, the association between metformin and outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF) is still unknown. We aimed to explore the association between metformin and adverse outcome in T2DM patients with HFpEF.Methods: A total of 372 T2DM patients with HFpEF hospitalized from January 1, 2013, to December 31, 2017, were included in this retrospective cohort study. There were 113 and 259 subjects in metformin and non-metformin group, respectively. Subjects were followed up for all-cause mortality, cardiovascular death, all-cause hospitalization, and heart failure hospitalization.Results: The median follow-up period was 47 months. Eleven patients (2.49% per patient-year) in the metformin group and 56 patients (5.52% per patient-year) in the non-metformin group deceased during follow-up (P = 0.031). However, a multivariable Cox regression failed to show that metformin was an independent factor of all-cause mortality [HR (95% CI) = 0.682 (0.346–1.345); P = 0.269]. A subgroup analysis revealed a significant association between metformin and all-cause mortality in patients with a higher hemoglobin A1c (HbA1c) level (HbA1c ≥7%) [HR (95% CI) = 0.339 (0.117–0.997); P = 0.045]. The 4-year estimated number needed to treat (NNT) with metformin compared with non-metformin for all-cause mortality was 12 in all populations and 8 in the HbA1c ≥7% subgroup.Conclusions: Metformin was not independently associated with clinical outcomes in patients with T2DM and HFpEF, but was associated with lower all-cause mortality in the subgroup of patients with poor glycemic control. Prospective, randomized controlled trials are needed to further verify these findings.

Background: Aortic stenosis (AS) is the most common valvular disease in developed countries. Until now, the specific timing of intervention for asymptomatic patients with severe aortic stenosis and preserved ejection fraction remains controversial.Methods: A systematic search of four databases (Pubmed, Web of science, Cochrane library, Embase) was conducted. Studies of asymptomatic patients with severe AS or very severe AS and preserved left ventricular ejection fraction underwent early aortic valve replacement (AVR) or conservative care were included. The end points included all-cause mortality, cardiac mortality, and non-cardiac mortality.Results: Four eligible studies were identified with a total of 1,249 participants. Compared to conservative management, patients who underwent early AVR were associated with lower all-cause mortality, cardiac mortality, and non-cardiac mortality rate (OR 0.16, 95% CI 0.09–0.31, P < 0.00001; OR 0.12, 95% CI 0.02–0.62, P = 0.01; OR 0.36, 95% CI 0.21–0.63, P = 0.0003, respectively).Conclusions: Early AVR is preferable for asymptomatic severe AS patients with preserved ejection fraction.

Background. The use of selective dorsal neurectomy (SDN) as a surgical treatment of premature ejaculation (PE) has increased for many years in Asian countries. Objectives.To investigate the correlation between age and curative effects of SDN in primary premature ejaculation (PPE) in mainland China. Materials and methods.From September 2016 to September 2020, 65 patients with PPE treated with SDN were selected for study. All of the patients were followed up from 12 to 56 (30.07 ±13.48) months. They were divided into 3 groups according to age: group A (22-30 years, n = 23), group B (31-37 years, n = 20) and group C (38-45 years, n = 22). The 5-item version of the International Index of Erectile Function (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) results, erectile rigidity grade, intravaginal ejaculation latency time (IELT), ejaculation control abilities (ECA) scores, and sexual intercourse satisfaction (SIS) scores were assessed in the 3 groups before and after operation to evaluate the clinical efficacy of surgery.Results. Fifty-nine patients were finally followed up. The IIEF-5 scores and erectile rigidity grade of group A was significantly higher than that of groups B and C, both before and after surgery. The change of PEDT scores in group A was significantly higher than in groups B and C; the difference was statistically significant (p < 0.05). The IELT, ECA and SIS scores in group A were significantly higher than in groups B and C (p < 0.05). Operational efficiency ratio in groups B and C (65%, 70%) was significantly lower than in group A (95.24%). Conclusions.The SDN as a treatment of PPE in different age groups allowed to achieve certain results. The highest surgical efficiency (95.24%) was observed in the 22-30 years age group and the lowest (65%) in the 38-45 years age group. Therefore, we believe that the best time for surgery is between 22 and 30 years of age.